The Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Cardiometabolic Risk Factors: A Systematic Review

Abstract

A large body of evidence supports the cardioprotective effects of the long-chain omega-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). There is increasing interest in the independent effects of EPA and DHA in the modulation of cardiometabolic risk factors. This systematic review aims to appraise the latest available evidence of the differential effects of EPA and DHA on such risk factors. A systematic literature review was conducted up to May 2017. Randomised controlled trials were included if they met strict eligibility criteria, including EPA or DHA > 2 g/day and purity ≥ 90%. Eighteen identified articles were included, corresponding to six unique studies involving 527 participants. Both EPA and DHA lowered triglyceride concentration, with DHA having a greater triglyceride-lowering effect. Whilst total cholesterol levels were largely unchanged by EPA and DHA, DHA increased high-density lipoprotein (HDL) cholesterol concentration, particularly HDL2, and increased low-density lipoprotein (LDL) cholesterol concentration and LDL particle size. Both EPA and DHA inhibited platelet activity, whilst DHA improved vascular function and lowered heart rate and blood pressure to a greater extent than EPA. The effects of EPA and DHA on inflammatory markers and glycaemic control were inconclusive; however both lowered oxidative stress. Thus, EPA and DHA appear to have differential effects on cardiometabolic risk factors, but these need to be confirmed by larger clinical studies.

Short‐term interleukin‐37 treatment improves vascular endothelial function, endurance exercise capacity, and whole‐body glucose metabolism in old mice

“…The ratio of L‐arginine to L‐citrulline tended to be higher in plasma from recIL‐37 vs. placebo‐treated mice, which also is consistent with greater NO synthesis. Moreover, we observed changes in metabolites that may reflect reduced inflammation and oxidative stress, including lower levels of cystine and kynurenine (González Esquivel et al, ) and higher levels of the cardioprotective free fatty acid DHA (Innes & Calder, ; Sakai et al, ). Indeed, supplementation with DHA, alone and in combination with eicosapentaenoic acid, improves NO‐mediated endothelial function in humans with CVD risk factors (Goodfellow, Bellamy, Ramsey, Jones, & Lewis, ; Mori et al, ; Rizza et al, ).…”

Rounding the corner on residual risk: Implications of REDUCE‐IT for omega‐3 polyunsaturated fatty acids treatment in secondary prevention of atherosclerotic cardiovascular disease

“…We now understand that there are substantial differences in their biological activities. 48 Thus, studies that combine the omega-3 PUFAs may fail to discern important health effects that are mostly due to one particular omega-3 PUFA.…”

“…Reported biological actions of EPA and DHA extend well beyond TG lowering and include effects expected to be cardioprotective . As summarized by Mozaffarian and Rimm, and shown in Figure , fish oil omega‐3 PUFAs have been linked with reduced blood pressure and heart rate, as well as decreased platelet aggregation .…”

“…When evaluating both observational and interventional studies of omega‐3 PUFAs, it is important, however, to consider whether the investigators have distinguished ALA, EPA, and, DHA. We now understand that there are substantial differences in their biological activities . Thus, studies that combine the omega‐3 PUFAs may fail to discern important health effects that are mostly due to one particular omega‐3 PUFA.…”

Involvement of polyunsaturated fatty acids in the control of energy storage and expenditure

“…In contrast to v6 PUFA excessive intake, it has been reported that diets enriched with v3 PUFAs or v3 LC-PUFAs lead to beneficial effects and contribute to improve of human health. Cohort analyses have shown normalization of inflammation, lowering plasma triglycerides and amelioration of the cardiovascular metabolic status (Duda et al, 2009;Innes and Calder, 2018). In rodents, inclusion of LNA in LA-rich high fat diet prevents the enhancement of fat mass (Massiera et al, 2003).…”